This invention relates to novel compositions of matter; and improved non-toxic carrier composition and more particularly it relates to improved pharmaceutical preparations providing for the release of pharmacologically active materials over a controlled extended period of time, methods of producing such preparations and stable aqueous emulsions derived therefrom.
It has now been found that a pharmaceutical oral dosage may be prepared in such a way as to enable the pharmacologically active material contained therein to be released on contact with the skin or to enable the active material contained therein to be released from the imbedded media or emulsion on ingestion at a retarded rate, thus prolonging the pharmacological activity and, at the same time, making it possible to accurately control the level of pharmacologically active material in the system so as to provide the desired effect. Among the inert components which are presently being used for such purposes are high molecular weight waxes, used singly or in various combinations, either evenly distributed among the active ingredients or first melted and then carefully coated over small particles of the active components (U.S. Pat. No. 2,918,411).
One disadvantge in the use of a wax for long-acting tablet formulations is that a relatively large mass of wax must be incorporated in the dosage form to give the desired long-acting effect. In other words, the ratio of wax to active component is a several-fold factor, thus requiring the manufacture of a bulky tablet such that its ingestion by patients is relatively difficult and uncomfortable.
It can be readily seen, however, that one of the prevailing problems in the pharmaceutical development field is the manufacture of controlled-release dosage forms which contain inert components that have large surface area, are nonabsorbable, and if absorbable, are substantially devoid of toxicity and undesirable side effects.
The use of alkaline earth metal salts of saturated fatty acids in tablet manufacture is known. These substances have been used for many years as tablet lubricants and fillers; they are incorporated into the final tablet granulation just prior to compression in relatively small quantities in order to facilitate compression of the granules without their adherence to the punches and dies in the tableting machine.
It is also known that saturated fatty acids, their esters, ethers and alcohols, can be pelletized with polyvinylpyrrolidone by converting the polymer, in the presence of the saturated fatty acid or its derivative, into a molten mass, granulating the congealed mss, reheating, cooling, adding the therapeutic component and pelletizing at a temperature near the set point.
It has now been surprisingly found that following the teachings of the instant invention, foods which are subjected to heat treatment in processing with an accompanying decrease in nutritive value due to partial or complete loss of carbohydrates, essential amino acids and vitamins may now be processed without losses. As is known, in order to compensate for the aforementioned losses, many nutritive components are added to food before processing is completed. Thus, most canned foods, evaporated milk products, dried protein products, cereals, and the like are fortified with amino acids, vitamins, etc. Some of these fortifying agents, however, are themselves affected by long periods (sterilization), light, moisture, oxygen or temperature of the environment.
Among the many disadvantages in using saturated fatty acids or their derivatives in combination with polyvinylpyrrolidone to prepare prolonged action dosage unit forms is their physical similarity to high molecular weight waxes. Because of their physical character, large quantities of the saturated fatty acid substance must be employed to obtain a desired effect. Thus, the proportion of polyvinylpyrrolidone to saturated fatty acid material must be about 1:7, or less. Moreover, it is known that saturated fatty acids themselves are inadequate as long acting vehicle agents, even though combined with polyvinylpyrrolidone. Thus, it has been equally necessary in order to obtain the desired prolonged effect, to incorporate a quantity of high molecular weight waxes, candelilla wax, bees wax or the like in the formulation. This adds further to the bulkiness of the dosage form, unnecessarily increasing the volume of the total mass and making the ingestion of same that much more difficult.
On the other hand, by using saturated fatty acid salts, while it is possible to decrease the ratio of salt to polyvinylprrolidone, one encounters the problem that there is an absence of complexing between the salt and the polyvinylprrolidone. This inherent drawback is immediately obvious where one seeks to produce an emulsion containing active ingredients, polyvinylpyrrolidone and a water insoluble hydrophobic chain end.